This proposal is for the 22nd to 26th years of the National Simulation Resource (NSR) in Circulatory Mass Transport at the University of Washington (UW). It concerns metabolic transformations and exchanges. It builds the concepts and modeling of intracellular events on top of the previously developed models, modeling systems and expertise on convection-diffusion-permeation-reaction systems. The five-year program will produce models from subcellular to whole-organ level for the inflow of substrates and humoral agents, the exchange across capillary and cell membranes, the metabolic transformations and the washout of metabolites. There are three scientific Sections and a set of Cores. Investigators from Vanderbilt, McGill, and Michigan State Universities contribute subcontractual projects. Investigators in 13 other universities and 4 countries contribute collaborative projects. There are 26 project leaders and 65 project investigators.Section D.I. concerns five developments in fundamental tools for Simulation Analysis in metabolic and humoral systems. The first is a major development of JSIM, a Java-based, integrative model simulation system designed for easy and collaborative model development. It improves upon the previous XSIM environment which was limited to Unix systems. New tools will be provided for simulating transport in complex geometries, for modeling of stochastic systems, for the application of biochemical circuit theory, and for databasing and modeling with a markup language. Section D.II. has three subsections (fifteen projects) defining particular modeling targets for UW on Whole-organ Transport, CellularTransport, Metabolism and Control, and Stochastic Cellular and Molecular Processes. Section D.III. consists of fourteen collaborative projects on Cardiac Flows and Metabolism, Cardiac Receptor Activity, Nucleoside and Nucleotide Regulation, Cellular Energetics, Cardiac Coronary Anatomy, and Cardiac Contraction and Metabolism. Section D.IV. provides core support for software development, simulation and modeling analysis, training, and the dissemination of NSR deliverables.